EP0991741B1 - WAX ESTERS ENRICHED IN $g(v)-3 UNSATURATED FATTY ACIDS, THEIR PREPARATION AND THEIR USE - Google Patents
WAX ESTERS ENRICHED IN $g(v)-3 UNSATURATED FATTY ACIDS, THEIR PREPARATION AND THEIR USE Download PDFInfo
- Publication number
- EP0991741B1 EP0991741B1 EP98932141A EP98932141A EP0991741B1 EP 0991741 B1 EP0991741 B1 EP 0991741B1 EP 98932141 A EP98932141 A EP 98932141A EP 98932141 A EP98932141 A EP 98932141A EP 0991741 B1 EP0991741 B1 EP 0991741B1
- Authority
- EP
- European Patent Office
- Prior art keywords
- fatty acids
- wax esters
- esters
- enriched
- wax
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 235000021122 unsaturated fatty acids Nutrition 0.000 title abstract description 10
- 150000004670 unsaturated fatty acids Chemical class 0.000 title abstract description 10
- 238000002360 preparation method Methods 0.000 title description 6
- 239000004164 Wax ester Substances 0.000 claims abstract description 45
- 235000019386 wax ester Nutrition 0.000 claims abstract description 45
- 239000000203 mixture Substances 0.000 claims abstract description 23
- 235000020660 omega-3 fatty acid Nutrition 0.000 claims abstract description 23
- MBMBGCFOFBJSGT-KUBAVDMBSA-N all-cis-docosa-4,7,10,13,16,19-hexaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCC(O)=O MBMBGCFOFBJSGT-KUBAVDMBSA-N 0.000 claims description 34
- JAZBEHYOTPTENJ-JLNKQSITSA-N all-cis-5,8,11,14,17-icosapentaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O JAZBEHYOTPTENJ-JLNKQSITSA-N 0.000 claims description 17
- 235000020669 docosahexaenoic acid Nutrition 0.000 claims description 17
- 229940090949 docosahexaenoic acid Drugs 0.000 claims description 17
- 235000020673 eicosapentaenoic acid Nutrition 0.000 claims description 17
- JAZBEHYOTPTENJ-UHFFFAOYSA-N eicosapentaenoic acid Natural products CCC=CCC=CCC=CCC=CCC=CCCCC(O)=O JAZBEHYOTPTENJ-UHFFFAOYSA-N 0.000 claims description 17
- 229960005135 eicosapentaenoic acid Drugs 0.000 claims description 17
- 150000002148 esters Chemical group 0.000 claims description 14
- 150000001298 alcohols Chemical class 0.000 claims description 12
- 235000021588 free fatty acids Nutrition 0.000 claims description 7
- -1 - stearyl- Chemical group 0.000 claims description 5
- 239000007787 solid Substances 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 3
- 235000013305 food Nutrition 0.000 claims description 3
- ALSTYHKOOCGGFT-KTKRTIGZSA-N (9Z)-octadecen-1-ol Chemical compound CCCCCCCC\C=C/CCCCCCCCO ALSTYHKOOCGGFT-KTKRTIGZSA-N 0.000 claims description 2
- 206010028980 Neoplasm Diseases 0.000 claims description 2
- 208000007536 Thrombosis Diseases 0.000 claims description 2
- 125000002252 acyl group Chemical group 0.000 claims description 2
- 230000002425 cardiocirculatory effect Effects 0.000 claims description 2
- 210000000987 immune system Anatomy 0.000 claims description 2
- 239000011159 matrix material Substances 0.000 claims description 2
- XMLQWXUVTXCDDL-UHFFFAOYSA-N oleyl alcohol Natural products CCCCCCC=CCCCCCCCCCCO XMLQWXUVTXCDDL-UHFFFAOYSA-N 0.000 claims description 2
- 229940055577 oleyl alcohol Drugs 0.000 claims description 2
- 201000010099 disease Diseases 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
- 208000035150 Hypercholesterolemia Diseases 0.000 claims 1
- 208000031226 Hyperlipidaemia Diseases 0.000 claims 1
- 206010061218 Inflammation Diseases 0.000 claims 1
- 125000002511 behenyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 230000004054 inflammatory process Effects 0.000 claims 1
- 239000004005 microsphere Substances 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 17
- 229940079593 drug Drugs 0.000 abstract description 3
- 238000009472 formulation Methods 0.000 abstract description 3
- 239000000546 pharmaceutical excipient Substances 0.000 abstract description 3
- 235000013373 food additive Nutrition 0.000 abstract description 2
- 239000002778 food additive Substances 0.000 abstract description 2
- 239000000047 product Substances 0.000 description 23
- 235000019441 ethanol Nutrition 0.000 description 18
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 125000004494 ethyl ester group Chemical group 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 239000002253 acid Substances 0.000 description 10
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 8
- 239000001993 wax Substances 0.000 description 8
- 150000007513 acids Chemical class 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 238000002844 melting Methods 0.000 description 7
- 230000008018 melting Effects 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 6
- 238000009835 boiling Methods 0.000 description 6
- NOPFSRXAKWQILS-UHFFFAOYSA-N docosan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCO NOPFSRXAKWQILS-UHFFFAOYSA-N 0.000 description 6
- 150000004665 fatty acids Chemical class 0.000 description 6
- 230000003647 oxidation Effects 0.000 description 6
- 238000007254 oxidation reaction Methods 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 235000014113 dietary fatty acids Nutrition 0.000 description 5
- 229930195729 fatty acid Natural products 0.000 description 5
- 239000000194 fatty acid Substances 0.000 description 5
- 235000021323 fish oil Nutrition 0.000 description 5
- 150000002632 lipids Chemical class 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 238000004809 thin layer chromatography Methods 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 102000004882 Lipase Human genes 0.000 description 3
- 239000004367 Lipase Substances 0.000 description 3
- 108090001060 Lipase Proteins 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 235000005911 diet Nutrition 0.000 description 3
- 230000000378 dietary effect Effects 0.000 description 3
- 235000019621 digestibility Nutrition 0.000 description 3
- 229960000735 docosanol Drugs 0.000 description 3
- 235000012631 food intake Nutrition 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000000968 intestinal effect Effects 0.000 description 3
- 229940119170 jojoba wax Drugs 0.000 description 3
- 235000019421 lipase Nutrition 0.000 description 3
- 229940012843 omega-3 fatty acid Drugs 0.000 description 3
- 239000006014 omega-3 oil Substances 0.000 description 3
- 210000000496 pancreas Anatomy 0.000 description 3
- 230000007170 pathology Effects 0.000 description 3
- 235000020777 polyunsaturated fatty acids Nutrition 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000005809 transesterification reaction Methods 0.000 description 3
- 150000003626 triacylglycerols Chemical class 0.000 description 3
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 125000003158 alcohol group Chemical group 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 229960000541 cetyl alcohol Drugs 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- BTFJIXJJCSYFAL-UHFFFAOYSA-N icosan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCO BTFJIXJJCSYFAL-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 150000002978 peroxides Chemical class 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 238000007127 saponification reaction Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- HLZKNKRTKFSKGZ-UHFFFAOYSA-N tetradecan-1-ol Chemical compound CCCCCCCCCCCCCCO HLZKNKRTKFSKGZ-UHFFFAOYSA-N 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
- RVBUGGBMJDPOST-UHFFFAOYSA-N 2-thiobarbituric acid Chemical compound O=C1CC(=O)NC(=S)N1 RVBUGGBMJDPOST-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 206010015137 Eructation Diseases 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- WSMYVTOQOOLQHP-UHFFFAOYSA-N Malondialdehyde Chemical group O=CCC=O WSMYVTOQOOLQHP-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000036983 biotransformation Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 150000003841 chloride salts Chemical class 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Natural products C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 1
- 102000005311 colipase Human genes 0.000 description 1
- 108020002632 colipase Proteins 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000004332 deodorization Methods 0.000 description 1
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 1
- 229960003964 deoxycholic acid Drugs 0.000 description 1
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 238000009884 interesterification Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000002085 irritant Substances 0.000 description 1
- 231100000021 irritant Toxicity 0.000 description 1
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008274 jelly Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 229940118019 malondialdehyde Drugs 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 235000021281 monounsaturated fatty acids Nutrition 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 238000003359 percent control normalization Methods 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000002344 surface layer Substances 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11C—FATTY ACIDS FROM FATS, OILS OR WAXES; CANDLES; FATS, OILS OR FATTY ACIDS BY CHEMICAL MODIFICATION OF FATS, OILS, OR FATTY ACIDS OBTAINED THEREFROM
- C11C3/00—Fats, oils, or fatty acids by chemical modification of fats, oils, or fatty acids obtained therefrom
- C11C3/04—Fats, oils, or fatty acids by chemical modification of fats, oils, or fatty acids obtained therefrom by esterification of fats or fatty oils
- C11C3/10—Ester interchange
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/115—Fatty acids or derivatives thereof; Fats or oils
- A23L33/12—Fatty acids or derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Veterinary Medicine (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Fats And Perfumes (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
Description
R" : methyl, ethyl, or a low boiling alcohol residue,
R' : residue of an alcohol contained in natural wax esters, provided that The esters of EPA and DHA are contained in this mixture in percentage higher than 18% and 12% respectively, corresponding to the percentages of these two acids usually found in natural products.
Peroxidability of wax esters (200 mg) in vitro in comparison with same amounts of fish oil. | ||
Time after incubation | Wax esters | Fish oil absorbance (thiobarbituric acid reaction substances, TBARS, malondialdehyde units) |
day 1 | 0.160 | 1.295 |
day 2 | 0.323 | 1.996 |
day 3 | 2.362 | 5.081 |
Effect of an acute treatment with wax esters (5 g/kg, oral) on plasma lipids of rats | |||
Time after treatment (h) | Cholesterol | Triglycerides | |
mg/d1±SD | |||
Control | - | 64.7 ± 1.5 | 82.2 ± 5.5 |
Wax esters | 6 | 60.0 ± 10.7 | 99.2 ± 6.9 |
Wax esters | 16 | 68.9 ± 2.2 | 129.0 ± 5.3 |
Effect of an acute treatment with wax esters (5 g/kg, oral) on the rat plasma content in fatty acids. | |||
Fatty acid | Control | Main plasma fatty acids (moles %) | |
6 hours after treatment | 16 hours after treatment | ||
12:0 | 0.2 | 0.2 | 0.2 |
14:0 | 0.5 | 0.3 | 0.5 |
15:0 | 0.3 | 0.2 | 0.5 |
16:0 | 21.0 | 13.6 | 20.4 |
18:0 | 13.7 | 12.6 | 8.8 |
18:1 | 14.9 | 8.1 | 14.2 |
18:2ω3 | 25.4 | 18.3 | 32.5 |
18:3ω3 | 1.7 | 1.1 | 2.1 |
20:2 | 0.1 | 1.0 | 0.8 |
20:3ω6 | 0.5 | 0.5 | 0.8 |
20:4ω6 | 9.7 | 13.4 | 6.3 |
20:5ω3 (EPA) | 2.3 | 6.1 | 2.4 |
22:2 | 1.5 | 5.9 | 1.1 |
22:4 | 0.4 | 4.6 | 1.8 |
22:5ω3 | 1.7 | 4.5 | 1.4 |
22 : 6ω3 (DHA) | 4.7 | 7.0 | 2.6 |
total ω6 | 37.0 | 42.2 | 41.7 |
total ω3 | 10.4 | 18.7 | 8.5 |
Effect of a subchronic treatment with wax ester (0.3 g/kg each day, for 15 days) on body weight, food consumption, and intestinal transit of rats. | ||||
Initial body weight | Final body weight | Food consumption Intestinal | ||
(g±SD) | g/rat/day | transit % | ||
Control | 174 ± 6.5 | 261 ± 4.0 | 31.0 | 48.0 |
Wax esters | 173 ± 4.0 | 261 ± 5.6 | 27.3 | 52.6 |
Example 1. 25 gr of an enriched fish oil ester (saponification value = 170 mg KOH/gr, average molecular weight 330, EPA 33%, DHA 22% as from gaschromatographic area percent analysis) was mixed with 25 gr of behenyl alcohol (molecular weight 326). The mixture was treated with 0.3 3 gr of sodium methoxide and the flask was connected to a vacuum pump (40 mbar). Temperature was raised up to 120°C. The stirred mixture darkened, as ethanol started boiling at ca. 80°C. A temperature of 120°C was maintained for half an hour. During this time, ethanol evolution almost ceased. The mixture was then cooled at 40°C, then the vacuum was removed by filling the flask with nitrogen. The liquid mixture was poured into a 1% aqueous solution of citric acid (200 ml) stirred under nitrogen at room temperature. Stirring was continued for five minutes at room temperature, then the mixture, still stirred, was cooled down to 5°C, whereby crystallization occurred. The solid material was filtered under vacuum, washed with water on the filter, and recrystallized from 400 ml of acetone. After cooling the mixture at -10°C for one hour, the whitish crystalline product was filtered under vacuum and dried under reduced pressure overnight at room temperature. Yield: 42.5 gr (89%). The product gives a clean spot in TLC (silica gel plates, eluting system; n-hexane-ethyl ether 9:1, Rf = 0.87, whereas Rf of the starting ethyl ester = 0.75, Rf of behenyl alcohol = 0.11). The melting point of the wax was 47°C.
Example 2. The same ethyl ester of example 1 (33 gr) was reacted with 27 gr of stearyl alcohol (molecular weight 270). Reaction conditions were the same as for example 1. Yield: 43.5 gr (67.5%), after crystallization from 200 ml of acetone. A clear spot in TLC was detected (silica gel, m-hexane-ethyl ether 49:1; Rf = 0.23). By superimposing this product with product of example 1, no separation can be observed. Melting point: 39°C.
Example 3. 25 gr of an ethyl ester enriched in EPA (74% EPA), with no DHA, (saponification value: 170, average molecular weight 330) were reacted with 25 gr of behenyl alcohol. Reaction conditions were the same as for example 1. The product obtained from water was not completely soluble even in large amounts of hot acetone, so it was filtered as it was a melted phase through a paper filter and dried under reduced pressure. Yield: 39.4 gr (82.7%): Melting point: 40°C.
Example 4. 25 gr of ethyl ester (the same as in Example 1) were reacted with 16.2 gr of 1-tetradecanol (molecular weight 214). Reaction conditions were the same as for example 1. After pouring the mixture into acidic water, the oily phase was washed twice at 45°C with 100 ml of water. After separation, the oily phase was then dried under reduced pressure. Yield: 35 gr (90%). Melting point: 23°C. Thin layer chromatography showed a neat spot, with the same Rf of the products of examples 1, 2, and 3.
Example 5. 33 gr of the same ethyl ester of example 1 (33% EPA, 22% DHA) were reacted by the same procedure of Example 1 with 24 gr of 1 hexadecanol (cetyl alcohol). The solid filtered from water at 3°C was stirred in 50 ml of cold acetone (at -10°C) for half an hour, then it was filtered under vacuum and dried under reduced pressure. Yield 47 gr (89%). Melting point 31°C.
Example 6. 33 gr of the same ethyl ester of example 1 were reacted with 29 gr of 1-eicosanol. After the same procedure and the same work up of example 1, 42 gr of wax ester were obtained (75%). Melting point 43°C.
Example 7. The same preparation described in Example 2 was repeated. Crystallization from acetone was omitted, but the raw product obtained after separation of the melted wax from hot water was washed again by the same procedure. A product was obtained, having the same melting point and the same purity as the one described in Example 2. The yield was raised to 96%.
Example 8. Digestibility test. The effect of pancreas lipase on wax esters has been verified according to the method by Neumann (U.Neumann, P.Kaspar, and J.Ziegenborn, "Methods in Enzymatic Analysis", Bergmayer HV, 1984, vol.4, pp.34-36). 800 mg of wax esters enriched in ω-3 polyunsaturated fatty acids, and, in parallel for a comparison, 800 mg of jojoba oil were incubated in a Tris buffer 0.125 M , pH 9.2, containing human pancreas lipase, colipase, and deoxycholic acid for different times at 37°C. After extraction of lipids, portions of organic phases containing lipids were dried and laid down on a silica gel TLC plate with concentration band. Plates were eluted with n-hexane-ethyl ether-acetic acid 80:20:1. Spot were visualized by exposure both to iodine and to sprayed sulphuric acid.
Claims (7)
- A composition of esters formed by free fatty acids enriched in ω-3 polyunsaturated fatty acids and alcohols occurring in natural wax esters, characterized in that the content of acyl residues of DHA (docosahexaenoic acid) and/or EPA (eicosapentaenoic acid) is higher than 12% and 18%, respectively.
- A composition according to claim 1, in which the alcohols are selected from the group consisting of behenyl, - stearyl-, tetradec-1-yl-, cetyl-, eicos-1-yl-, oleyl alcohol.
- A composition according to claim 1, for use as a medicament.
- A composition according to claim 3, for use in the treatment of cardio-circulatory diseases, thrombosis, platelet hyperaggregation, hyperlipidemia, hypercholesterolemia, inflammation, cancer, diseases of the immune system.
- Use of the composition of claim 1 as dietary-alimentary integrator.
- Dietary-alimentary integrators containing the composition of claim 1.
- Dietary-alimentary integrators according to claim 6, in the form of microspheres or absorbed onto a solid matrix used as food.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IT97MI001369A IT1292126B1 (en) | 1997-06-11 | 1997-06-11 | WAX ESTERS ENRICHED IN UNSATURATED OMEGA-3 FATTY ACIDS, THEIR PREPARATION AND USE |
ITMI971369 | 1997-06-11 | ||
PCT/EP1998/003466 WO1998056883A1 (en) | 1997-06-11 | 1998-06-09 | WAX ESTERS ENRICHED IN φ-3 UNSATURATED FATTY ACIDS, THEIR PREPARATION AND THEIR USE |
Publications (2)
Publication Number | Publication Date |
---|---|
EP0991741A1 EP0991741A1 (en) | 2000-04-12 |
EP0991741B1 true EP0991741B1 (en) | 2002-11-27 |
Family
ID=11377334
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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EP98932141A Expired - Lifetime EP0991741B1 (en) | 1997-06-11 | 1998-06-09 | WAX ESTERS ENRICHED IN $g(v)-3 UNSATURATED FATTY ACIDS, THEIR PREPARATION AND THEIR USE |
Country Status (11)
Country | Link |
---|---|
US (1) | US6274751B1 (en) |
EP (1) | EP0991741B1 (en) |
AT (1) | ATE228556T1 (en) |
AU (1) | AU740719B2 (en) |
CA (1) | CA2293367C (en) |
DE (1) | DE69809743T2 (en) |
DK (1) | DK0991741T3 (en) |
IT (1) | IT1292126B1 (en) |
NO (1) | NO312163B1 (en) |
NZ (1) | NZ501690A (en) |
WO (1) | WO1998056883A1 (en) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0910955A3 (en) * | 1997-10-24 | 2000-03-22 | Unilever N.V. | Wax ester compositions |
US7557228B2 (en) * | 2004-12-30 | 2009-07-07 | Universiti Putra Malaysia | Production of wax esters |
JP2012514596A (en) * | 2009-01-05 | 2012-06-28 | カラナス エーエス | Bio-oil composition, formulation containing said oil composition and use thereof for prevention or treatment of cardiovascular disease |
CA2765329C (en) * | 2009-06-12 | 2018-01-02 | Calanus As | Oil composition, formulations comprising the oil composition, and the use thereof to reduce accumulation of visceral fat, improve glucose tolerance, and prevent or treat obesity related diseases and disorders |
SG11201608898UA (en) * | 2014-04-25 | 2016-12-29 | Yamada Bee Co Inc | Unsaturated fatty acid absorption accelerator |
IT201700054543A1 (en) * | 2017-05-19 | 2018-11-19 | Gleaner Srls | Prepared as a source of Omega-3 |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DK565288D0 (en) * | 1988-10-11 | 1988-10-11 | Novo Industri As | PROCEDURE FOR THE PREPARATION OF TRIGLYCERIDES, APPLICATION OF SUCH TRIGLYCERIDES, AND AN EMULSION CONTAINING SUCH TRIGLYCERIDES |
WO1992022631A1 (en) * | 1991-06-11 | 1992-12-23 | Beku Environmental Products Ltd. | Degreaser composition comprising monounsaturated wax ester |
US5463143A (en) * | 1994-11-07 | 1995-10-31 | Shell Oil Company | Process for the direct hydrogenation of wax esters |
JP2562009B2 (en) * | 1995-03-02 | 1996-12-11 | 日清製粉株式会社 | Docosahexaenoic acid glyceride |
-
1997
- 1997-06-11 IT IT97MI001369A patent/IT1292126B1/en active IP Right Grant
-
1998
- 1998-06-09 AU AU82148/98A patent/AU740719B2/en not_active Ceased
- 1998-06-09 WO PCT/EP1998/003466 patent/WO1998056883A1/en active IP Right Grant
- 1998-06-09 US US09/445,419 patent/US6274751B1/en not_active Expired - Lifetime
- 1998-06-09 DE DE69809743T patent/DE69809743T2/en not_active Expired - Lifetime
- 1998-06-09 EP EP98932141A patent/EP0991741B1/en not_active Expired - Lifetime
- 1998-06-09 DK DK98932141T patent/DK0991741T3/en active
- 1998-06-09 CA CA002293367A patent/CA2293367C/en not_active Expired - Fee Related
- 1998-06-09 NZ NZ501690A patent/NZ501690A/en not_active IP Right Cessation
- 1998-06-09 AT AT98932141T patent/ATE228556T1/en active
-
1999
- 1999-12-09 NO NO19996074A patent/NO312163B1/en not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
ATE228556T1 (en) | 2002-12-15 |
NZ501690A (en) | 2001-10-26 |
AU8214898A (en) | 1998-12-30 |
WO1998056883A1 (en) | 1998-12-17 |
DE69809743T2 (en) | 2003-09-04 |
IT1292126B1 (en) | 1999-01-25 |
DE69809743D1 (en) | 2003-01-09 |
US6274751B1 (en) | 2001-08-14 |
DK0991741T3 (en) | 2003-03-24 |
EP0991741A1 (en) | 2000-04-12 |
NO996074D0 (en) | 1999-12-09 |
CA2293367C (en) | 2006-10-03 |
CA2293367A1 (en) | 1998-12-17 |
AU740719B2 (en) | 2001-11-15 |
NO312163B1 (en) | 2002-04-02 |
ITMI971369A1 (en) | 1998-12-11 |
ITMI971369A0 (en) | 1997-06-11 |
NO996074L (en) | 2000-02-11 |
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